AP3D1

Chr 19AR

adaptor related protein complex 3 subunit delta 1

Also known as: ADTD, HPS10, hBLVR

NCBI Gene: 8943 ENSG00000065000 UniProt: O14617 OMIM: 607246

The AP3D1 protein is a subunit of the AP-3 adaptor complex that facilitates vesicle budding from the Golgi membrane and trafficking to lysosomes, playing a critical role in the formation and transport of pigment granules, platelet dense granules, and neurotransmitter vesicles. Mutations cause Hermansky-Pudlak syndrome 10, a multisystem disorder affecting pigmentation, bleeding, and potentially neurological function, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is not tolerated in the general population.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a subunit of the AP3 adaptor-like complex, which is not clathrin-associated, but is associated with the golgi region, as well as more peripheral structures. The AP-3 complex facilitates the budding of vesicles from the golgi membrane, and may be directly involved in trafficking to lysosomes. This subunit is implicated in intracellular biogenesis and trafficking of pigment granules, and possibly platelet dense granules and neurotransmitter vesicles. Defects in this gene are a cause of a new type of Hermansky-Pudlak syndrome. [provided by RefSeq, Feb 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Hermansky-Pudlak syndrome 10MIM #617050

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · Hermansky-Pudlak syndrome 10 · AR · ClinGen 2025

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — AP3D1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.986

Z-score 5.97

OE 0.18 (0.11–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.94Z-score

OE missense 0.80 (0.75–0.86)

603 obs / 753.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.11–0.30)

0≤0.351.4

Missense OE?0.80 (0.75–0.86)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 11 / 61.5Missense obs/exp: 603 / 753.2Syn Z: -2.24

Background carrier burden — how many people carry a rare variant somewhere in AP3D1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,593 rare PASS variants

Rare truncating (LoF)

1 in 2,300

113 rare PASS variants

Rare synonymous (reference)

1 in 52

791 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AP3D1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 49	1 in 2,900
South Asian	~43k	1 in 31	1 in 3,900
Remaining (unassigned)	~30k	1 in 35	1 in 1,600
European (Finnish)	~27k	1 in 100	1 in 1,700
Admixed American	~22k	1 in 39	1 in 1,000
African / African American	~21k	1 in 37	1 in 570
East Asian	~20k	1 in 38	1 in 3,900
Ashkenazi Jewish	~13k	1 in 280	1 in 1,600
Middle Eastern	~2,884	1 in 35	≈ 1 in 950

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 31 of 32 coding exons well covered in gnomAD exomes; exon 23 marginal. Genomes: all 32.? see exons ↓